Project Summary The fifth Gordon Research Conference (GRC) on Notch Signaling in Development, Regeneration & Disease (July 19 ? July 23, 2020 at Bates College, Maine) will address a major unmet need in the American scientific community by convening scientists from both academia and industry around a fundamentally important developmental signaling pathway broadly relevant to health and disease. Although the first ?Notch phenotype? was described over a century ago, studies elucidating the molecular events responsible for Notch signal transduction have accelerated since the early 1980s after cloning of the Drosophila Notch receptor gene. Subsequent studies showed that Notch signaling requires cell-cell contact, established that ligand-induced proteolysis of the Notch receptor produces a transcriptional regulator that stimulates expression of target genes, and demonstrated that post-translational modifications are critical to modulate ligand-receptor interactions. Studies in model organisms identified the importance of Notch signaling in numerous cell fate decisions. Human genetic studies showed that mutations of core Notch pathway components underlie several developmental syndromes (e.g. Alagille Syndrome, Spondylocostal Dysostosis, aortic valve disease) and adult onset diseases (e.g. CADASIL, various heart and valve malformations), while causing or contributing to cancer initiation or progression in a tissue-dependent manner. Beyond its role in specific organ systems, new findings have also uncovered a role for Notch in immune, inflammatory and metabolic disorders. Notch-targeted antibodies and pathway inhibitors have entered clinical trials as potential anti-cancer therapeutics and are being considered for other indications, but effective deployment of Notch modulators in the clinic continues to pose distinct challenges around efficacy (what tumors or disease states are most likely to respond), and toxicity, because of the importance of Notch in the homeostasis of selected adult tissues (such as the gut). Building on past success, this meeting aims to provide a vibrant US forum to stimulate cross disciplinary discussions and collaborations in this important area of biology, nurture a sense of community among researchers, and welcome new members into the field. The meeting program will bring together scientists from academia, biotech and the pharmaceutical industry addressing fundamental mechanistic, developmental, clinical and therapeutic questions using cutting-edge approaches. Invited participants include a blend of established ?thought leaders? with vast institutional memory and many early career scientists with exciting new findings. The informal and confidential environment in GRC meetings encourages free scientific exchange of unpublished data. The inclusion and integration of a Gordon Research Seminar (GRS) exclusively for postdocs and graduate students prior to the GRC is a particular asset to draw new scientists into the field and encourage trainee participation. Most importantly, the combined GRC/GRS format excels in integrating students, postdocs and investigators wishing to enter a new field, such as the study of this important signaling pathway.